Over the past 6 years, we have established a unique, NIH funded, Clinical Research Center focused on the physiology of middle ear (ME) pressure (MEP) regulation. The integrating theme is the role played by MEP disregulation (MEPD) in the pathogenesis of otitis media (OM) with effusion (OME). We are requesting 5 years of NIH support to further develop this research theme. We include three Projects supported by two Cores. Project 1 evaluates MEP-regulation during health and disease, defines the diagnostic utility of current and newly developed methods to assess MEP-regulation, explores those physiological mechanisms that potentially modulate MEP-regulation and initiates the transfer of these tests and results to the clinical environment. Project 2 is a continuation of an ongoing, 5-year follow-up of three groups of children who were entered at 3 years of age with a documented history of chronic OME, recurrent acute OM or no significant OM. For each group, we are following the children to 7-8 years of age with repeated evaluations of MEP-regulation using standardized test protocols and periodic measures of the anatomy of the Eustachian tube (ET)/ME system. These data will be used to define the differences in ET/ME anatomy and function between groups at each age, the changes in anatomy and function for each group with growth and development, and the effect of the anatomical substrate on function. The goals are to determine if any anatomic or functional measure predicts group assignment and if any of the measures predict the future course of disease in a given child. Project 5 continues our work on modeling MEP-regulation for normal and diseased MEs. These models are used to develop functional-anatomic relationships, to aid in the interpretation of data from the Projects and to define possible treatment options for OME. Core A administers the Center, guides its future direction and provides data entry and statistical services to all Projects. Core B develops new tests, protocols and instruments to assess MEP-regulation and provides all testing/imaging services required by the three Projects. This Clinical Research Center is unique in its focus on MEP-regulation and the role played by MEPD in OME pathogenesis.